{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:03:14Z","timestamp":1784782994649,"version":"3.55.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The updated SOFA-2 score excludes the immune system due to specificity concerns, creating a conceptual gap given that sepsis is defined by a dysregulated host response. We hypothesized that augmenting SOFA-2 with widely available immune markers\u2014white blood cell counts, lymphocyte counts, and the neutrophil-to-lymphocyte ratio (NLR)\u2014would improve mortality prediction in patients with suspected infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 75,203 adult patients from the MIMIC-IV, MIMIC-III, and eICU databases. We constructed an immune-augmented SOFA-2 model using provisional consensus criteria for cell counts and data-driven thresholds for NLR derived via generalized additive models. Discrimination was evaluated using random-effects meta-analysis of the area under the receiver operating characteristic (AUROC) curve and net reclassification improvement (NRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The immune-augmented model significantly outperformed standard SOFA-2 across all cohorts. In the pooled analysis, the immune-augmented SOFA-2 yielded a higher AUROC (0.750 [95% CI, 0.715\u20130.785]) compared to standard SOFA-2 (0.740 [95% CI, 0.712\u20130.768]; p=0.003). Additionally, incorporating immune markers improved clinical risk stratification, resulting in a significant pooled total NRI of 0.046 (95% CI, 0.014\u20130.078; p=0.005).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Excluding the immune system limits the ability of the SOFA-2 score to capture the dysregulated host response essential to severe infection. Integrating immune markers significantly enhances prognostic accuracy and risk reclassification for patients with suspected infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1904045","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:30:44Z","timestamp":1784781044000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Augmenting SOFA-2 with immune markers to capture dysregulated host response in patients with suspected infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Yu","family":"Qi","sequence":"first","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Sun","sequence":"additional","affiliation":[{"name":"Heze Hospital Affiliated to Shandong First Medical University, Heze Municipal Hospital","place":["Heze, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Hou","sequence":"additional","affiliation":[{"name":"Heze Hospital Affiliated to Shandong First Medical University, Heze Municipal Hospital","place":["Heze, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.20516","article-title":"Development and validation of the sequential organ failure assessment (SOFA)-2 score","volume":"334","author":"Ranzani","year":"2025","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2025.45040","article-title":"Rationale and methodological approach underlying the development of the sequential organ failure assessment (SOFA)-2 score: a consensus statement","volume":"8","author":"Moreno","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"Jama"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-025-01004-6","article-title":"The immunology of sepsis: translating new insights into clinical practice","volume":"22","author":"Kox","year":"2026","journal-title":"Nat Rev Nephrol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40779-020-00267-3","article-title":"Comparison of clinical laboratory tests between bacterial sepsis and SARS-CoV-2-associated viral sepsis","volume":"7","author":"Ren","year":"2020","journal-title":"Mil Med Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkaa040","article-title":"Predictive value of immune cell counts and neutrophil-to-lymphocyte ratio for 28-day mortality in patients with sepsis caused by intra-abdominal infection","volume":"9","author":"Liu","year":"2021","journal-title":"Burns Trauma"},{"key":"B7","volume-title":"Mimic-Iv","author":"Johnson","year":"2024"},{"key":"B8","volume-title":"MIMIC-III Clinical Database Carevue Subset","author":"Johnson","year":"2022"},{"key":"B9","volume-title":"The eICU collaborative research database","author":"Pollard","year":"2017"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"Jama"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1904045\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:30:56Z","timestamp":1784781056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1904045\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":10,"alternative-id":["10.3389\/fimmu.2026.1904045"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1904045","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1904045"}}